■Romosozumab是一种新型的与硬化蛋白结合的单克隆抗体,具有增加骨形成和减少骨吸收的双重作用,赋予它独特的作用机制。这项研究的目的是基于随机对照试验中关于romosozumab治疗效果和安全性的现有全球数据进行系统评价和荟萃分析。
■对包括PubMed在内的四个数据库进行了系统搜索,Embase,WebofScience和Cochrane中央对照试验登记册(CENTRAL)。用于搜索的关键词是“(romosozumab)和(骨质疏松症或安全性)”。包括研究romosozumab的效果和安全性的随机对照试验或纳入的随机对照试验的事后研究。使用Cochrane协作工具和PEDro量表评估选定研究的质量。
■20项研究被纳入定性分析。纳入14项研究进行荟萃分析。总的来说,有13,507名(n=13,507)参与者,637名男性和12,870名女性来自原始队列.总体平均差异有利于romosozumab治疗腰椎(10.04(95%置信区间(CI)=7.51-12.57;p<0.00001)),12个月时的全髋关节(4.04(95%CI=3.10-4.99;p<0.00001))和股骨颈骨密度(3.77(95%CI=2.90-4.64;p<0.00001))。在治疗12个月时,与对照组相比,使用romosozumab发生新的椎骨骨折的可能性显着降低(比值比(OR)0.42(95%CI=0.20-0.89;p=0.02)。与仅使用抗再吸收剂的对照相比,使用romosozumab治疗12个月后出现新的椎骨骨折的可能性显着降低(OR0.36(95%CI=0.18-0.71);p=0.003)。在我们的荟萃分析中,与对照组相比,使用romosozumab的严重不良事件和致命不良事件没有显着差异。romosozumab的亚洲人群与对照组的严重心血管事件没有显着差异,对照组使用romosozumab治疗12个月,然后使用24个月的抗吸收剂,OR为1.09(95%CI=0.40-2.96;P=0.86)。Romosozumab组和对照组在放射学愈合的中位时间上没有显着差异。我们对定量计算机断层扫描(QCT)的定性分析,有限元分析(FEA)和骨活检分析表明,romosozumab也改善了这些领域的参数和措施。
■总而言之,我们的研究表明,romosozumab是治疗骨质疏松症的有效药物,具有高质量的证据。不良事件无显著差异,严重不良事件,确定的致命不良事件。在总人口中心血管事件和心血管死亡的进一步亚组分析显示也没有差异。
■给定结果,romosozumab是治疗骨质疏松性骨折高危患者的有效药物.
UNASSIGNED: Romosozumab is a novel monoclonal antibody that binds to sclerostin, and has dual effects of increasing bone formation and decreasing bone resorption, giving it a unique mechanism of action. The objective of this study was to perform a systematic review and meta-analysis based on existing worldwide data on treatment effects and safety of romosozumab in randomized controlled trials.
UNASSIGNED: A systematic search was carried out on four databases including PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The keywords used for search was \"(
romosozumab) AND (osteoporosis OR safety)\". Randomized controlled trial or post-hoc studies of the included randomized controlled trial which studied the effects and safety of romosozumab were included. The quality of selected studies was assessed with the Cochrane collaboration tool and the PEDro scale.
UNASSIGNED: 20 studies were included for qualitative analysis. 14 studies were included for meta-analysis. In total, there were 13,507 (n = 13,507) participants with 637 men and 12,870 women from original cohorts. The overall mean difference was in favor of romosozumab treatment for lumbar spine (10.04 (95 % confidence interval (CI) = 7.51-12.57; p < 0.00001)), total hip (4.04 (95 % CI = 3.10-4.99; p < 0.00001)) and femoral neck bone mineral density (3.77 (95 % CI = 2.90-4.64; p < 0.00001)) at 12 months. There was significantly less likelihood of new vertebral fractures with
romosozumab compared to control (odds ratio (OR) 0.42 (95 % CI = 0.20-0.89); p = 0.02) at 12 months of treatment. There was significantly less likelihood of new vertebral fracture at 24 months with 12 months of romosozumab followed by sequential treatment with anti-resorptive compared to control with only anti-resorptive agent use (OR 0.36 (95 % CI = 0.18-0.71); p = 0.003). There was no significant difference in serious adverse events and fatal adverse events with use of romosozumab compared with control in our meta-analyses. There were no significant differences in serious cardiovascular events in Asian population of romosozumab with control group with 12 months of
romosozumab treatment followed by 24 months of anti-resorptive agent with OR 1.09 (95 % CI = 0.40-2.96; P = 0.86). There was no significant difference between
romosozumab group and control group for the median time to radiographic healing. Our qualitative analysis on Quantitative Computed Tomography (QCT), Finite element analysis (FEA) and bone biopsy analyses demonstrated that romosozumab improved parameters and measures in these domains as well.
UNASSIGNED: In conclusion, our study showed that romosozumab was an effective agent to treat osteoporosis with high quality evidence. There were no significant differences in the adverse events, serious adverse events, fatal adverse events identified. Further subgroup analysis of cardiovascular events and cardiovascular death in the total population showed no differences either.
UNASSIGNED: Given the results, romosozumab is an effective agent to treat patients with very-high risk of osteoporotic fractures.